2-p-dialkylaminoalkoxyphenyl-2, 3-dihydro-4 (1h)-quinazolinones and their derivatives



3,265,697 Z-p-DHALKYLAMINOALKOXYPHENYL 2,3 DIHY- DRO-4(1H)-QUINAZOLINONES AND THEIR DE- RIVATIVES Edgar S. Schipper, Clifton, N.J., assignor to Shulton, Inc., Clifton, NJ, a corporation of New Jersey No Drawing. Filed Sept. 4, 1964, Ser. No. 394,604 8 Claims. (Cl. 260256.4)

This invention relates to 2-p-dialkylam-inoallcoxyphenyl- 2,3-dihydro-4(lH)-quin azolinones and their non-toxic salts.

The 2-p-dialkylaminoalkoxyphenyl-2,3-dihydro-4(1H)- quinazolinones of this invention are new compounds havtates Patent 3,265,697 Patented August 9, 1966 Non-toxic salts of the 2-p-dial kylaminoalkoxyphenyl- 2,3-dihydro-4(lH)-quinaz0linones of this invention are produced by mixing equimolecular amounts of the required 2-p-dialkylaminoalkoxyphenyl-2,3-dihy-d-ro-4(1H)- quinazolinones and the required acid in an inert solvent such as ether, ethanol, benzene or toluene, and subsequently filtering the precipitated salt or evaporating the solvent Salts of inorganic acid such as hydrochloric, sulfiuric or phosphoric acid or salts of organic acids such as acetic, succinic, tartaric or ascorbic acid of the 2-p-dialkylaminoalkoxyphenyl-2,B-dihydro-4(lH)-quinazolinones may be produced in this maning the following formula:

1'1 R and recovering the salt residue.

-O(CH2)nN R N-Ri R i ner. 0

in which R, is hydrogen, lower alkyl, cycloalkyl, allyl, aralkyl, aryl or substituted aryl in which the substituent is lower alkyl or halogen; R is hydrogen or halogen, R and R is hydrogen or lower alkyl and n is a whole number from 1 to 3. Examples of lower alkyl are those containing less than 6 carbon atoms, such as methyl. An example of cycloalkyl is cyclopropyl, that of an aralkyl is homoveratryl, that of an aryl is phenyl and that of a substituted aryl is tolyl or chlorophenyl.

The compounds of this invention manifest central neryous system stimulant activity in mammals at dosages from 10 to 300 mg. per kg. of body weight. Such dosages are significantly lower than the respective LD of such compounds.

The new 2-p-d-ialkylamin0allcoxyphenyl-2,3-dihydro- 4(1H)- quinazolinones of this invention may be produced by reacting in the presence of a base, such as an alkali metal hydroxide, a substituted anthranilamide with the required aldehyde in accordance with the following reac- A more comprehensive understanding of this invention is obtained by reference to the following examples:

Examples 1-7 2,3 dihydro 2 p 5 diethylaminoethoxyphenyl 6 chloro-4( 1H -quinazolinone;

2,3 dihydro 2 p [i diethylaminoethoxyphenyl 3 allyl-4(1H)-quinaz,olinone;

2,3 dihydro 2 p 5 diethylaminoethoxyphenyl 3 homoveratryl-6-ehloro-4( 1H -quinazolinone;

2,3 dihydro 2 p B diethylaminoethoxyphenyl 3 o-tolyl-4( lH)-quinazolinone;

2,3 di'hydro 2 p B diethylaminoethoxyphenyl 3-p-chl0rophenyl-4( lH)-quinazollnone;

2,3 dihydro 2 p B diethylaminoethoxyphenyl 3 et-hyl-6-chloro-4( 1H -quinazolinone;

2,3 dihydro 2 p [i diethylaminoethoxyphenyl 3 cyclopropyl-4( 1H -quinazolinone.

Each of the above 2-p-dialkylaminoalkoxyphenyl-2,3- dihydro-4(lH)-quinazolinones was prepared by refluxing for two hours a solution of 0.1 M 22.1 g.) of p fi-diethyl- NH H Ra aminoethoxybenzaldehyde in 100 ml. of ethanol and 0.1 OWE) 011- M of the anthranilamide intermediate required and de- R GONHR noted in the following Table I. A solution of ml. of RI 8% sodium hydroxide was added and the mixture was TABLE I Exa. Z-P-dialkylamlnonlknxyphenyl-2,3- Anthranilaniide intermediate used diliydro-4(1H)-quinnzolinoncs produced 1 2am dm-Z-p-fl-diethylamino-eth- 5-chloroanthrsmilarnide.

oxyp 1enyi-6-chloro-4(lib-quintuolinone.

2 .c 2,3-dihydro-2-p-fl-diethylamino-eth- 2-amino-N-allyl-beuzamlde.

0xyphenyl-3-a1lyl-4(lib-quinazolinone.

3 2,3dlhydroJ-nB-diethylamino-eth- Z-amino-Ecl1l0ro-N-homoveratryloxyphenyl-3-homoveratryl-tichlorobenzamlde. 4(1li)-quinazolinone.

4 2,3-dihydro-Z-p-fl-diethyl-nminoeth- Z-amlno-N-o-tolyl-benimnide.

oxyphenyl-3 otolyl-4(1H)-quinazolinone.

5 2,3-dihydro-2-p-fi-dlethyl-aminoeth- Z-amino-N-p-chloro-phenyl-benzoxypllenyl-3-p-chloro-phenyl-4(1H)- amide. quinazolinone.

6 2,B-dihydreZ-pfl-diethyl-aminoeth- Z-amino-5-chloro-N-ethylbenznmide.

oxyphenyl-3-ethyl-6-ehloro-4(1H)- quinnzolinone.

7 2,3-dillydro-Zp-fi-diethyl-aminoeth- 2-amino-N-eyelo-propylbenzamlde.

oxyphenyl-S-cyelo-propyl-4(1H)- quinazollnone.

3 heated 011 the steam bath for -30 minutes. The reaction product crystallized from the solution when it was placed in the refrigerator for 2-24 hours. The product was filtered otf and recrystallized.

The following Table II shows the solvent used in recrystallization of the final product, the melting point, analysis of carbon, hydrogen and nitrogen, as calculated and found, and the percent yield of each of the Z-p-dialkylaminoalkoxyphenyl 2,3 dihydro 4(1H) quinazogen; R is selected from the group consisting of hydrogen and halogen; R and R are selected from the group consisting of hydrogen and lower alkyl; and n is a whole number from 1 to 3.

2. 2,3 dihydro 2 p 3 diethylaminoethoxyphenyl- 6-chloro-4( 1H) -quinazolinone.

3. 2,3 dihydro 2 p 3 diethylaminoethoxyphenyl- 3-allyl-4( lH)-quinazolinone.

4. 2,3 dihydro 2 p 3 diethylaminoethoxyphenyllinones produced by the practice of each of the examples. 10 3-homovera'tryl-6-chloro-4(lH)-quinazolinone.

TABLE II Analysis Solvent Used in Recrys- Example lllzatlon M.P., 0. Calculated Found Yield,

' percent;

0 II N C H N Ethyl acetate 185486 64. 6. 47 11. 24 64. 39 6. 69 11. 12 72 Ether- 122-124 72. 79 7. 11.07 73. 00 7. 75 ll. 28 98 Ethyl acetatelhexane 114-116 66. 6. 75 7. 81 67. 21 6. 7. 57 71 Methanol- 1904 91 75. 49 7. 27 9. 78 75. 49 7. 39 9. 87 76 Ethyl acetate- 69. 40 6. 27 9. 34 69. 34 6. 10 9. 09 81 d 65. 74 7. 02 10. 45 65. 79 7. 12 10. 59 85 do 72. 79 7. 70 11.07 72. 07 7. 42 10. 96 40 in which R is selected from the group consisting of hydrogen, lower alkyl, cyclo lower alkyl, allyl, homoverat'ryl, phenyl and substitute/d pheny'l in which the substituent is selected from the group consisting of lower alkyl and ha1o- 5. 2,3 dihydro 2 p fl diethylaminoethoxyphenyl- 3-o-tolyl-4( 1H -quin azolinone.

5. 2,3 dihydro 2 p ,8 diethylaminoethoxyphenyl- 3-p-chlorophenyl-4(1H)-quinazolinone.

7. 2,3 dihydro 2 p B diethylaminoethoxyphenyl- 30 3-ethyl-6-chloro-4 lH)-quinazolinone.

8. 2,3 dihydro 2 p B diethylaminoethoxyphenyl- 3-cyclopropyl-4( 1H -qu inazolinone.

References Cited by the Examiner Bohme et al., Archiv der Pharm, vol. 293, No. 11, 1960, pages 1011-1020.

Elderfield, Heterocyclic Compounds, vol. 6, New York, John Wiley & Sons, Inc., page 346.

40 HENRY R. JILES, Acting Primary Examiner.

MARY E. OBRIEN, Assistant Examiner. 

1. A COMPOUND SELECTED FROM THE CLASS CONSISTING OF 2P-DIALKYLAMINOALKOXYPHENYL -2,3 - DIHYDRO-4(1H)-QUINAZOLINONES AND NON-TOXIC ACID ADDITION SALTS THEREOF, SAID 2P-DIALKYLAMINOALKOXYPHENYL - 2,3 - DIHYDRO-4(1H-QUINAZOLINONES HAVING THE FORMULA: 